Upregulated microRNA-485 suppresses apoptosis of renal tubular epithelial cells in mice with lupus nephritis via regulating the TGF-β-MAPK signaling pathway by inhibiting RhoA expression.

Lupus nephritis (LN) is a common and severe complication of systemic lupus erythematosus. Without intervention, LN may cause acute kidney injury and end-stage renal disease. This study aims to determine whether microRNA-485 (miR-485) affects renal tubular epithelial cells (RTECs) in LN mice via the TGF-β-MAPK signaling pathway by targeting RhoA. Renal tissue samples were initially extracted from 15 LN and 15 normal mice. RTECs were cultivated in vitro and grouped after transfection of different mimics, inhibitors, or siRNA- RhoA. The target gene of miR-485 was confirmed by dual-luciferase reporter assay. Flow cytometry and MTT assay were applied to detect cell viability and apoptosis. It was determined that RhoA was a target gene of miR-485. We found that urine protein, creatinine, RhoA, interleukin 6 (IL-6), transforming growth factor-β1 (TGF-β1), and p38 mitogen-activated protein kinases (p38MAPK) were highly expressed in renal tissues of LN mice, while poor levels of miR-485 were recorded. The overexpression of miR-485 or siRNA- RhoA or the combination of miR-485 and siRNA- RhoA was demonstrated to lead to a reduction of levels of RhoA, IL-6, TGF-β, and p38MAPK, as well as a promotion of RTECs proliferation and inhibition of RTECs apoptosis. Taken together, these findings indicated that overexpressed miR-485 downregulates RhoA which could promote cell viability and inhibit apoptosis of RTECs by regulating the RhoA-mediated TGF-β-MAPK signaling pathway in LN mice.